1. Bioengineering and World Health Lecture Four: Leading Causes of Mortality, Ages 45-60 Global Health Challenges Geoff Preidis MD/PhD candidate Baylor College of Medicine preidis@post.harvard.edu

2. Developing World 1. HIV/AIDS 2. Unintentional injuries 3. Cardiovascular diseases 4. Tuberculosis Developed World 1. Unintentional injuries 2. Cardiovascular diseases 3. Cancer 4. Self-inflicted injuries Summary of Lecture 3: Leading Causes of Mortality Ages 15-44

3. 1. HIV/AIDS While working at an outreach clinic in Africa, you encounter a critically ill adolescent who tests positive for HIV. How can you estimate the severity of this patient’s disease? What classes of pharmaceuticals are available to treat this patient?

4. 2. Unintentional Injuries Do unintentional injuries account for more deaths in developed or developing countries? Give several reasons why.

5. 3. Cancer and Cardiovascular Diseases Will be discussed today!

6. 4. Tuberculosis If your next PPD skin test is positive, what will your doctor do next?

7. 4. Self-Inflicted Injuries What disease ranks #1 in DALYs in developed countries? How can we prevent these injuries?

8. Lecture 4: Leading Causes of Mortality Ages 45-60 Developing World 1. Cardiovascular diseases 2. Cancer (malignant neoplasms) 3. Unintentional injuries 4. HIV/AIDS Developed World 1. Cardiovascular diseases 2. Cancer (malignant neoplasms) 3. Unintentional injuries 4. Digestive Diseases

9. 1. Cardiovascular Diseases 70ml per beat… 1.3 gallons per minute… 1,900 gallons per day… 700,000 gallons per year… 48 million gallons by age 70…

10. 1. Cardiovascular Diseases Burden of Cardiovascular Diseases Ischemic Heart Disease Epidemiology Pathogenesis Diagnosis Treatment Cerebrovascular Disease Epidemiology Pathogenesis Diagnosis Treatment

11. Burden of Cardiovascular Diseases: Ages 15-44 768,000 people ages 15-44 die as a result of cardiovascular disease every year Most common causes: Ischemic heart disease (286,000 deaths) Cerebrovascular disease (159,000 deaths)

12. 2 million people ages 45-60 die as a result of cardiovascular disease every year Most common causes: Ischemic heart disease (1 million deaths) Cerebrovascular disease (625,000 deaths) Burden of Cardiovascular Diseases: Ages 45-60

13. Ischemic Heart Disease: Epidemiology United States 12 million people have coronary artery disease Causes more deaths, disability and economic cost than any other illness Risk factors Positive family history Diabetes Hyperlipidemia Hypertension Smoking

14. Ischemic Heart Disease: Pathogenesis Atherosclerosis Causes decrease in myocardial perfusion Most common symptom is angina Stable angina (75% lumen blockage) Typically a 50-60 yo man or 65-75 yo woman Heaviness, pressure, squeezing, smothering or choking Localized to chest, may radiate to left shoulder and arms Lasts 1-5 minutes Unstable angina (more than 80% blockage) Patients with angina that is: New onset and severe and frequent Accelerating Angina at rest

15. Evolution of a heart attack: 1.Endothelial injury 2.Fatty deposits 3.Fibrous cap with necrotic core 4.Unstable plaques rupture, thrombogenic core causes blood clots 5.Blood clots can lead to complete occlusion 6.Heart muscle supplied by occluded artery dies 7.If patient survives, affected heart muscle is replaced by scar tissue Ischemic Heart Disease: Pathogenesis In the US, 30% of patients do not survive a first heart attack For 50% of CAD patients, their first symptom is a heart attack

16. Ischemic Heart Disease: Diagnosis Usually made by history Physical exam may reveal other disorders Lipid disorders Hypertension Diabetes Testing EKG Stress Testing Coronary arteriography

17. http://www.columbiasurgery.org/divisions/cardiac/im ages/novartis_207B.jpg

18. Ischemic Heart Disease: Treatment Medical management (may relieve symptoms of CAD, but does not reduce coronary blockage) Nitrates Increase myocardial oxygen supply, systemic vasodilation Beta blockers Inhibit increases in heart rate and contractility Decrease myocardial oxygen demand Calcium channel antagonists Coronary vasodilators Thrombolysis CABG (Coronary Artery Bypass Grafting) PTCA (Percutaneous Transluminal Coronary Angioplasty)

19. CABG

20. PTCA

21. Cerebrovascular Disease: Epidemiology Third leading cause of death in the US Most prevalent neurologic disorder 87% caused by ischemia and resulting infarction

22. Cerebrovascular Disease: Pathogenesis Causes of stroke: Blood vessel supplying the brain is blocked Thrombosis (clot in vessel) Embolism (clot breaks off and lodges in blood vessel in brain) Vasoconstriction or spasm Venous collapse

23. Cerebrovascular Disease: Pathogenesis Abrupt onset with focal neurologic deficit Usually mini-event or warning signs 15% Transient Ischemic Attacks (TIAs) Reversible ischemia Some lasting 24-72 hours Completed stroke Maximal deficit within hours Often patient awakens with completed stroke Usually preceded by TIA Progressive stroke Ischemia worsens min. to min. or hour to hour

24. Cerebrovascular Disease: Diagnosis History Exam Imaging CT Scan MRI MR Angiography

25. Cerebrovascular Disease: Diagnosis

26. Cerebrovascular Disease: Treatment Thrombolysis Rehabilitation Experimental Angioplasty Heparin Coumarin Aspirin

27. 2. Cancer Cancer Overview Burden of Cancer Pathogenesis of Cancer Cancer Diagnosis Treatment of Cancer Cancer and Infectious Diseases Lung Cancer Epidemiology Clinical Manifestations Treatment

28. Cancer Overview Cancer is a group of diseases characterized by uncontrolled cell growth Cancer cells usually form a tumor Abnormal mass of tissue Growth exceeds that of normal tissue Purposeless and preys on host Two types of tumors: Benign, Malignant Disease results from: Abnormal growth, loss of normal function Invasion, compression of adjacent tissues Metastases to distant sites in the body

29. Burden of Cancer 2nd leading cause of death in US 1 of every 4 deaths is from cancer Nearly 1/2 of all men and 1/3 of all women will develop cancer at some point in their lives 5-year survival rate: 59% Annual costs: $107 billion

30. Cancer kills 580,000 people ages 15-44 each year throughout the world Most common causes, ages 15-44: Liver Cancer (68,000 deaths per year) Leukemias (65,000) Stomach Cancer (58,000) Breast Cancer (57,000) Burden of Cancer, Ages 15-44

31. Burden of Cancer, Ages 45-60 Cancer kills 1.5 million people ages 45-60 each year throughout the world Most common causes, ages 45-60: Lung cancer (263,000 deaths per year) Stomach cancer (185,000) Liver cancer (179,000) Breast cancer (148,000)

32. 2007 Estimated US Cancer Deaths Source: American Cancer Society, 2007. Men 291,270 Women 273,560 26%Lung & bronchus 15%Breast 10%Colon & rectum 6%Ovary 6%Pancreas 4%Leukemia 3%Non-Hodgkin lymphoma 3%Uterine corpus 2%Multiple myeloma 2%Brain/other nervous system 23% All other sites Lung & bronchus31% Prostate9% Colon & Rectum9% Pancreas6% Leukemia4% Esophagus4% Liver & intrahepatic 4% bile duct Non-Hodgkin3% lymphoma Urinary bladder3% Kidney3% All other sites24%

33. Pathogenesis of Cancer Natural history of most cancers include sequential phases: Malignant transformation in target cell Growth of transformed cells Local invasion Distant metastases

34. Pathogenesis of Cancer Malignant Transformation, AKA Carcinogenesis: Result of non-lethal genetic damage Carcinogens, hereditary defects, or both Tumor masses result from the clonal expansion of a single progenitor cell that has incurred genetic damage Often, the host immune system is able to detect and eliminate the abnormally proliferating cells. But when these cells escape destruction…

35. Pathogenesis of Cancer

36. How do tumors invade? Detach from primary tumor Degrade surrounding matrix Migrate via blood or lymphatic vessels Metastasis causes 90% of cancer death

38. Cancer Diagnosis Benign tumors Well differentiated Dysplasia Precancerous condition in epithelial tissue Anaplastic cells in epithelium Dysplasia does not always progress to cancer Malignant tumors Range from well to poorly differentiated Anaplasia: Cells and nuclei show pleomorphism Cells contain abundant DNA, coarse, clumped chromatin Large NC ratio (1:1) rather than 1:4 or less Large nucleoli Large # of mitoses

39. Cancer Diagnosis

40. Normal Pap smearCervical cancer

41. Treatment of Cancer Surgical excision The most effective therapy, IF the entire tumor can be resected 90% 5-year survival Often, metastasis has already occurred Radiation/Chemotherapy Side effects

42. Importance of Cancer Screening

43. Cancer and Infectious Diseases Worldwide 15-20% of cancers are linked to infectious diseases These cancers can be avoided by preventing the infection associated with them HPV, cervical cancerHBV, liver cancer H. pylori, stomach cancer

44. 3. Unintentional Injuries More than 618,000 people ages 45-60 die from unintentional injuries each year Leading cause is road accidents: 222,000 deaths per year in this age group Covered in Lecture 3

45. 4. HIV/AIDS In the developing world, causes 386,000 deaths in people ages 45-60 per year Covered in Lecture 3

46. 4. Digestive Diseases Burden of digestive diseases Normal liver Cirrhosis Hepatitis

47. Burden of Digestive Diseases Worldwide, 456,000 people aged 45-60 die each year from digestive diseases Cirrhosis of the liver Kills 250,000 people each year between the ages of 45 and 60

48. Normal Liver Largest organ in the body Metabolizes fat and glucose Helps remove toxic substances from blood Produces: Bile to help absorb fats Proteins that regulate blood clotting Immune agents Loss of liver function can produce severe disease and death

49. Normal Liver

50. Cirrhosis Normal liver is replaced with scar tissue as a result of chronic injury, interfering with liver function Causes of cirrhosis: Chronic alcoholism Viral hepatitis infection Symptoms of cirrhosis: Exhaustion, loss of appetite, nausea, vomiting blood, weakness, weight loss, and abdominal pain. Patients bruise and bleed easily and become highly sensitive to medicines with increasing loss of liver functions. Diagnosis: needle biopsy

51. Hepatitis Infection which can also lead to cirrhosis Caused by hepatitis viruses A, B, C, D, and E HBV most common worldwide HCV most common in the US Acute HBV infection leads to chronic hepatitis in 5%, some of whom will develop cirrhosis Acute HCV infection leads to chronic hepatitis in 80%, 30% of whom will develop cirrhosis Vaccines available for HAV, HBV

52. Summary of Lecture Four Developing World 1. Cardiovascular diseases 2. Cancer (malignant neoplasms) 3. Unintentional injuries 4. HIV/AIDS Developed World 1. Cardiovascular diseases 2. Cancer (malignant neoplasms) 3. Unintentional injuries 4. Digestive Diseases

53. Leading Causes of Death Ages 0-4: Perinatal conditions Lower respiratory infections Diarrheal diseases Malaria Perinatal conditions Congenital anomalies Lower respiratory infections Unintentional injuries Ages 15-44: HIV/AIDS Unintentional injuries Cardiovascular diseases Tuberculosis Unintentional injuries Cardiovascular disease Cancer Self-Inflicted Injuries Ages 45-59: Cardiovascular diseases Cancers Unintentional injuries HIV/AIDS Cardiovascular diseases Cancer Unintentional injuries Digestive Diseases

54. Structural Violence

57. “It’s not just a treaty… it may well become the international Magna Carta” --Eleanor Roosevelt Structural Violence

58. ARTICLE 25 Everyone has the right to a standard of living adequate for the health and well- being of himself and of his family, including food, clothing, housing and medical care, and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control. ARTICLE 27 Everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits. Everyone has the right to the protection of the moral and material interests resulting from any scientific, literary or artistic production of which he is the author. Structural Violence

59. New World of Global Health Bill and Melinda Gates Foundation $14.4 billion since 1999 to global health issues August 24, 2006 gift from Warren Buffett Exceeds the WHO budget during the same time Global Fund to Fight AIDS, TB and Malaria $10 billion to 136 countries since 2002 President’s Emergency Plan for HIV/AIDS Relief (PEPFAR) $18.8 billion since 2004

60. Challenges Faced Countries struggle with procurement policies, hard to convert $$ to drugs Shortages of trained health care workers See The World Health Report 2006, WHO Corruption Lack of coherent approach

61. What is a Grand Challenge in Global Health? Scientific or technical innovation that: Removes a critical barrier to solving an important health problem in developing world High likelihood of global impact and feasibility Different than: Simple statement of a “big problem” in global health HIV/AIDS, malnutrition, lack of access to medical care, lack of resources Meant to: Direct investigators to specific breakthrough that provides solution to a significant health problem(s) See http://www.gcgh.org/

62. Grand Challenges in Global Health $200 million medical research initiative Bill and Melinda Gates Foundation National Institutes of Health (NIH) Encourage scientific and technological solutions to diseases that disproportionately affect the developing world Announced in January 2003

63. Call for Grand Challenges Call For Ideas I (May 2003) 1048 submissions from scientists and institutions in 75 countries Scientific Board heard proposals (August 2004) Problem Roadblock (obstacle to progress) Challenge List of potential benefits Funding increased to $450 million

64. Goals and Grand Challenges Seven Long Range Goals 14 Grand Challenges Heavily oriented toward infectious disease Infectious diseases account for the most profound discrepancies between advanced and developing economies Causes of infectious diseases are well-known Can more easily formulate technical and scientific obstacles to progress

65. Grand Challenge Proposals NIH issued request for proposals to address challenges Grants of up to $20M over five years or less http://www.gcgh.org/ Results reported in Science (Oct 17, 2003)

68. Closing Thoughts

72. Warmly Recommended Reading Mountains Beyond MountainsThe End of PovertyGuns, Germs, and Steel by Tracy Kidder by Jeffrey Sachs by Jared Diamond